e21699 Background: Olanzapine was found to be effective for preventing acute and delayed emesis in patients receiving highly emetogenic chemotherapy by randomized phase 3 study. However, there is limited data for the efficacy of olanzapine combined with palonosetron and dexamethasone in patients receiving moderately emetogenic chemotherapy (MEC). Methods: We conducted randomized, double-blind, placebo-controlled study to determine whether olanzapine could reduce the frequency of CINV and improve quality of life (QOL) in patients receiving palonosetron and dexamethasone for the prophylaxis of MEC induced nausea and vomiting. Two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. The primary end point was the complete response (no emesis and no use of rescue medication) for the acute phase (0-24 hours after chemotherapy). Secondary end points included the complete responses for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant emesis (VAS ≥ 25 mm) for overall phase, use of rescue medications, and effect on QOL by Functional Living Index-Emesis (FLIE) questionnaire. Results: Fifty-six patients were randomized and fifty-four patients were evaluable (29 assigned to olanzapine, and 25 to placebo). The complete response rate was not significant between olanzapine and placebo group in the acute (96.5% vs. 88.0%, P = 0.326), delayed (69.0% vs. 48.0%, P = 0.118), and overall phase (69.0% vs. 48.0%, P = 0.118). However, the percentage of patients with significant emesis (17.2% vs. 44.0%, P = 0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, P = 0.002) were significantly lower with olanzapine than with placebo in the overall phase. Furthermore, olanzapine group experienced a better QOL than the placebo group, as reported on the FLIE questionnaire (P = 0.015). Conclusions: Olanzapine in addition to palonosetron and dexamethasone significantly improved the management of emesis and QOL among previously untreated patients receiving MEC, although the efficacy was limited to reduce the frequency of CINV. Clinical trial information: NCT02400866.